CN105294568B - A kind of method for preparing benzimidazolone - Google Patents
A kind of method for preparing benzimidazolone Download PDFInfo
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- CN105294568B CN105294568B CN201510895738.3A CN201510895738A CN105294568B CN 105294568 B CN105294568 B CN 105294568B CN 201510895738 A CN201510895738 A CN 201510895738A CN 105294568 B CN105294568 B CN 105294568B
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- reaction
- benzimidazolone
- phenylenediamine
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- catalyst
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/26—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
Abstract
The present invention relates to a kind of new method for preparing benzimidazolone, in the presence of a catalyst, prepares benzimidazolone by o-phenylenediamine and dimethyl carbonate reaction under organic solvent boiling point, the methanol of by-product can be by simply condensing recycling.The present invention does cyclizing agent using dimethyl carbonate, and caused accessory substance is easy to absorb, and does not produce waste water；Realize that reaction mass is carried out in homogeneous reaction system, reaction mass is sufficiently mixed；Reaction temperature is constant, and easily controllable without regulation pH value, reaction；Solvent time is used, and is realized green and is combined to, product yield reaches 98.5%, and purity reaches 99.0%.
Description
Technical field
The invention belongs to chemical intermediate preparation field, and in particular to a kind of new method for preparing benzimidazolone.
Background technology
Benzimidazolone is important organic intermediate, is particularly applied to the fields such as medicine, pigment and agricultural chemicals.
In J.Am.Chem.Soc.80, document disclosed in 1657 (1958), there is provided one kind o-phenylenediamine and phosgene
The method that reaction prepares benzimidazolone.But phosgene used in the method has the danger of height, the pair of generation is reacted in addition
Product hydrogen chloride has very strong corrosivity to equipment.
Itd is proposed by patent US-4269989 and CN-9411729.9, o-phenylenediamine and urea are reacted in water, control temperature
Degree, using sour adjustment control pH 4 to 9, prepares benzimidazolone at 90 DEG C to 120 DEG C, unstable due to reacting, and causes to receive
Rate is unstable, and substantial amounts of waste water causes to pollute environment.
By patent US-4138568, it is known that making o-phenylenediamine class compound and urea and urea derivative have in water-insoluble
Reacted in solvent, wherein temperature is at 100 DEG C to 200 DEG C.But if the method as described in there, o-phenylenediamine and urea are having
Reacted in solvent, in the case of being added without phase transfer catalyst, the yield and purity of gained benzimidazolone be not high.
The method that patent US4138568 discloses the synthesizing benzimidazole ketone in dichloro-benzenes, o-phenylenediamine and Urea
Reacted 2 hours to 172 DEG C, obtain benzimidazolone, then to pass through complicated purification process, solvent consumption is big, produces a large amount of
Waste liquid.
Use phosgene or urea is for the shortcomings that cyclizing agent technique：
1st, phosgene has that the danger of height and byproduct of reaction hydrogen-chloride etching equipment are serious, unsuitable industrialized production；
2nd, the substantial amounts of ammonia of urea technique by-product is, it is necessary to which substantial amounts of water absorbs, so as to produce substantial amounts of waste water；
3rd, urea technique, due to residual of the ammonia in mother liquor, cause smell in production process larger.
The content of the invention
It is an object of the invention in view of the foregoing defects the prior art has, there is provided a kind of simple process, in high yield, it is high
The new method for preparing benzimidazolone of purity.In the presence of a catalyst, by o-phenylenediamine with dimethyl carbonate organic molten
Reaction prepares benzimidazolone under agent boiling point, and the methanol of by-product can avoid producing largely by simply condensing recycling
Waste water, and extraordinary yield and purity can be obtained, yield reaches 98.5%, purity ＞ 99.0%, mother liquor time
With rear, reused by being simply distilled to recover organic solvent, reach greenization production.
The chemical equation that benzimidazolone is prepared in the present invention is as follows：
The technical solution adopted for the present invention to solve the technical problems is：A kind of new method for preparing benzimidazolone, bag
Include following steps：
1) in the presence of a catalyst, o-phenylenediamine heats up in organic solvent with dimethyl carbonate occurs ring-closure reaction, obtains
Reaction solution；
2) reaction terminate after, reaction solution is down to room temperature, filtering, with the new organic solvent washing of identical in step 1), do
It is dry to obtain benzimidazolone.
Specifically, the temperature of ring-closure reaction is 110-180 DEG C in the step 1), and the reaction time is 4-10 hours.
Specifically, the mass ratio of dimethyl carbonate and o-phenylenediamine is 0.876~1.251 in the step 1)：1.
Specifically, the mass ratio of catalyst and o-phenylenediamine is 0.001~0.005 in the step 1)：1.
Specifically, catalyst is the one or more in TEBA, TBAC or polyethylene glycol in the step 1).
Specifically, organic solvent and o-phenylenediamine mass ratio are 3~10 in the step 1)：1.
Specifically, the organic solvent in the step 1) is in toluene, dimethylbenzene, chlorobenzene, dichloro-benzenes, DMF or DMSO
It is one or more.
Specifically, by-product carbinol therein is reclaimed in the condensed processing of reaction solution after reaction terminates in the step 1).
Reaction temperature is about limited to 180 DEG C, but in order that reacts the sufficiently fast of progress, temperature should be higher than that 130 DEG C.In addition,
Reacted at ambient pressure, overvoltage is unfavorable for the discharge of by-product carbinol, the volatilization of vacuum influence reaction temperature and solvent.
A kind of preferred embodiment of this method is in the presence of phase transfer catalyst TEBA, makes o-phenylenediamine and carbonic acid
Dimethyl ester reacts in chlorobenzene, and temperature control is more than 130 DEG C.When doing AABI products, a step and two step solvents system are realized
One, after isolating product from reaction solution, it is not necessary to dry the nitration reaction that can directly carries out next step.
After isolating benzimidazolone from reaction solution, a part of product also relevant with its solubility stays in mother liquor
In.In the method, high selectivity reaction allows mother liquor on the premise of product quality is significantly reduced instead of organic molten
Agent uses.Further it can significantly reclaim the product contained in mother liquor after reaction in this approach, hence it is evident that improve yield.
Products therefrom typically sloughs the mother liquor of adhesion, clean product benzimidazole ketone with a small amount of organic solvent washing
Dried when needing, it is not necessary to when directly do in next step react.Mother liquor and cleaning solution time are distilled to recover solvent, this method after
Waste water is not produced actually.
The invention has the advantages that：The present invention does cyclizing agent using dimethyl carbonate, and caused accessory substance is easy to
Absorb, do not produce waste water；Realize that reaction mass is carried out in homogeneous reaction system, reaction mass is sufficiently mixed；Reaction temperature
Spend constant and easily controllable without regulation pH value, reaction；Solvent time is used, and is realized green and is combined to, product yield reaches
98.5%, purity reaches 99.0%.
Embodiment
It is the specific embodiment of the present invention below, technical scheme is described further, but the present invention
Protection domain is not limited to these embodiments.It is every to be included in the present invention without departing substantially from the change of present inventive concept or equivalent substitute
Protection domain within.
Embodiment 1
In the 1000ml three-necked flasks equipped with electric stirring, reflux condensing tube and thermometer, 94.6g carbonic acid diformazans are added
Ester, 108g o-phenylenediamines, 324g chlorobenzenes and 0.108g phase transfer catalyst TEBA, it is warming up to solid and all dissolves, open stirring
It is continuously heating to 130 DEG C, reaction system was in 130 DEG C of insulation reactions 4 hours.Reaction is finished, and is down to room temperature, is filtered, and chlorobenzene washing, is done
It is dry to obtain 132g off-white color products, yield 98.5%, purity 99.5%.
Influence of the mother liquid recycle to product yield and purity see the table below：
| Apply mechanically number | Yield (%) | Purity (%) |
| 1 | 99.2 | 99.4 |
| 2 | 99.3 | 99.3 |
| 3 | 99.2 | 99.2 |
| 4 | 99.4 | 99.1 |
| 5 | 99.2 | 99.1 |
| 6 | 99.3 | 99.0 |
As can be seen from the above table, purity and yield impact very little of the mother liquid recycle to product.Solvent repeatedly can directly cover
With.
Embodiment 2
In the 1000ml three-necked flasks equipped with electric stirring, reflux condensing tube and thermometer, 94.6g carbonic acid diformazans are added
Ester, 108g o-phenylenediamines, 1080g toluene and 0.108g phase transfer catalyst TEBA, it is warming up to solid and all dissolves, unlatching is stirred
Mix and be continuously heating to 110 DEG C, reaction system was in 110 DEG C of insulation reactions 8 hours.Reaction is finished, and is down to room temperature, is filtered, toluene washing,
It is dried to obtain 142g off-white color products, yield 98.7%, purity 99.0%.
Embodiment 3
In the 1000ml three-necked flasks equipped with electric stirring, reflux condensing tube and thermometer, 94.6g carbonic acid diformazans are added
Ester, 108g o-phenylenediamines, 324gDMSO and 0.324g phase transfer catalyst TEBA, it is warming up to solid and all dissolves, open stirring
It is continuously heating to 150 DEG C, reaction system was in 150 DEG C of insulation reactions 4 hours.Reaction is finished, and is down to room temperature, is filtered, and DMSO washings, is done
It is dry to obtain 132g off-white color products, yield 98.6%, purity 99.8%.
Embodiment 4
In the 1000ml three-necked flasks equipped with electric stirring, reflux condensing tube and thermometer, 135.1g carbonic acid two is added
Methyl esters, 108g o-phenylenediamines, 540g dimethylbenzene and 0.54g phase transfer catalyst polyethylene glycol, it is warming up to solid and all dissolves,
Open stirring and be continuously heating to 180 DEG C, reaction system was in 180 DEG C of insulation reactions 10 hours.Reaction is finished, and is down to room temperature, filtering two
Toluene washs, and is dried to obtain 132g off-white color products, yield 98.7%, purity 99.5%.
Embodiment 5
In the 1000ml three-necked flasks equipped with electric stirring, reflux condensing tube and thermometer, 125g carbonic acid diformazans are added
Ester, 108g o-phenylenediamines, 540g DMF and 0.4g phase transfer catalyst TBAC, be warming up to solid all dissolve, open stirring after
Continuous to be warming up to 150 DEG C, reaction system was in 150 DEG C of insulation reactions 6 hours.Reaction is finished, and is down to room temperature, and filtering DMF is washed, dry
To 132.5g off-white color products, yield 98.9%, purity 99.8%.
Claims (7)
- A kind of 1. method for preparing benzimidazolone, it is characterised in that comprise the following steps：1) in the presence of a catalyst, o-phenylenediamine heats up in organic solvent with dimethyl carbonate occurs ring-closure reaction, must react Liquid；2) after reaction terminates, reaction solution is down to room temperature, filtering, with identical organic solvent washing in step 1), dry benzo Imidazolone；Catalyst is the one or more in TEBA, TBAC or polyethylene glycol in the step 1).
- 2. the method according to claim 1 for preparing benzimidazolone, it is characterised in that ring-closure reaction in the step 1) Temperature be 110-180 DEG C, the reaction time is 4-10 hours.
- 3. the method according to claim 1 for preparing benzimidazolone, it is characterised in that carbonic acid diformazan in the step 1) The mass ratio of ester and o-phenylenediamine is 0.876~1.251：1.
- 4. the method according to claim 1 for preparing benzimidazolone, it is characterised in that in the step 1) catalyst with The mass ratio of o-phenylenediamine is 0.001~0.005：1.
- 5. the method according to claim 1 for preparing benzimidazolone, it is characterised in that organic solvent in the step 1) It is 3~10 with o-phenylenediamine mass ratio：1.
- 6. the method for benzimidazolone is prepared according to claim 1 or 5, it is characterised in that having in the step 1) Solvent is the one or more in toluene, dimethylbenzene, chlorobenzene, dichloro-benzenes, DMF or DMSO.
- 7. the method according to claim 1 for preparing benzimidazolone, it is characterised in that reaction terminates in the step 1) By-product carbinol therein is reclaimed in the condensed processing of reaction solution afterwards.
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Denomination of invention: A method for preparing benzimidazolone Effective date of registration: 20211130 Granted publication date: 20171117 Pledgee: Dongying Hekou District sub branch of China Post Savings Bank Co.,Ltd. Pledgor: SHANDONG HUIHAI PHARMACEUTICAL& CHEMICAL Co.,Ltd. Registration number: Y2021980013568 |